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Background The primary objective of the study is to describe the cellular characteristics of bronchoalveolar lavage fluid (BALF) of COVID-19 patients requiring invasive mechanical ventilation; the secondary outcome is to describe BALF findings between survivors vs non-survivors. Materials and methods Patients positive for SARS-CoV-2 RT PCR, admitted to ICU between March and April 2020 were enrolled. At ICU admission, BALF were analyzed by flow cytometry. Univariate, multivariate and Spearman correlation analyses were performed. Results Sixty-four patients were enrolled, median age of 64 years (IQR 58–69). The majority cells in the BALF were neutrophils (70%, IQR 37.5–90.5) and macrophages (27%, IQR 7–49) while a minority were lymphocytes, 1%, TCD3+ 92% (IQR 82–95). The ICU mortality was 32.8%. Non-survivors had a significantly older age ( p  = 0.033) and peripheral lymphocytes ( p  = 0.012) were lower compared to the survivors. At multivariate analysis the percentage of macrophages in the BALF correlated with poor outcome (OR 1.336, CI95% 1.014–1.759, p  = 0.039). Conclusions In critically ill patients, BALF cellularity is mainly composed of neutrophils and macrophages. The macrophages percentage in the BALF at ICU admittance correlated with higher ICU mortality. The lack of lymphocytes in BALF could partly explain a reduced anti-viral response.

CAR− CD4+ T cell lymphopenia is an emerging issue following CAR‐T cell therapy. We analyzed the determinants of CD4+ T cell recovery and a possible association with survival in 31 consecutive patients treated with commercial CAR‐T for diffuse large B‐cell (DLBCL) or mantle cell lymphoma. Circulating immune subpopulations were characterized through multiparametric‐flow cytometry. Six‐month cumulative incidence of CAR− CD4+ T cell recovery (≥200 cells/μL) was 0.43 (95% confidence interval [CI]: 0.28–0.65). Among possible determinants of CD4+ T cell recovery, we recognized infusion of a 4‐1BB product (tisagenlecleucel, TSA) in comparison with a CD28 (axicabtagene/brexucabtagene, AXI/BRX) (hazard ratio [HR] [95% CI]: 5.79 [1.16–24.12] p = 0.016). Higher CD4+ T cell counts resulted with TSA at month‐1, ‐2 and ‐3. Moderate‐to‐severe infections were registered with prolonged CD4+ T cell lymphopenia. Early, month‐1 CD4+ T cell recovery was associated with a worse outcome in the DLBCL cohort, upheld in a multivariate regression model for overall survival (HR: 4.46 [95% CI: 1.12–17.71], p = 0.03). We conclude that a faster CAR− CD4+ T cell recovery is associated with TSA as compared to AXI/BRX. Month‐1 CAR− CD4+ T cell subset recovery could represent a “red flag” for CAR‐T cell therapy failure in DLBCL patients.

Immune checkpoint inhibitors (CI) have demonstrated clinical activity in Hodgkin Lymphoma (HL) patients relapsing after autologous stem cell transplantation (ASCT), although only 20% complete response (CR) rate was observed. The efficacy of CI is strictly related to the host immune competence, which is impaired in heavily pre-treated HL patients. Here, we aimed to enhance the activity of early post-ASCT CI (nivolumab) administration with the infusion of autologous lymphocytes (ALI). Twelve patients with relapse/refractory (R/R) HL (median age 28.5 years; range 18-65), underwent lymphocyte apheresis after first line chemotherapy and then proceeded to salvage therapy. Subsequently, 9 patients with progressive disease at ASCT received early post-transplant CI supported with four ALI, whereas 3 responding patients received ALI alone, as a control cohort. No severe adverse events were recorded. HL-treated patients achieved negative PET scan CR and 8 are alive and disease-free after a median follow-up of 28 months. Four patients underwent subsequent allogeneic SCT. Phenotypic analysis of circulating cells showed a faster expansion of highly differentiated NK cells in ALI plus nivolumab-treated patients as compared to control patients. Our data show anti-tumor activity with good tolerability of ALI + CI for R/R HL and suggest that this setting may accelerate NK cell development/maturation and favor the expansion of the “adaptive” NK cell compartment in patients with HCMV seropositivity, in the absence of HCMV reactivation.

Background Mass spectrometry (MS) is producing high volumes of data supporting oncological sciences, especially for translational research. Most of related elaborations can be carried out by combining existing tools at different levels, but little is currently available for the automation of the fundamental steps. For the analysis of MALDI/TOF spectra, a number of pre-processing steps are required, including joining of isotopic abundances for a given molecular species, normalization of signals against an internal standard, background noise removal, averaging multiple spectra from the same sample, and aligning spectra from different samples. In this paper, we present Geena 2, a public software tool for the automated execution of these pre-processing steps for MALDI/TOF spectra. Results Geena 2 has been developed in a Linux-Apache-MySQL-PHP web development environment, with scripts in PHP and Perl. Input and output are managed as simple formats that can be consumed by any database system and spreadsheet software. Input data may also be stored in a MySQL database. Processing methods are based on original heuristic algorithms which are introduced in the paper. Three simple and intuitive web interfaces are available: the Standard Search Interface, which allows a complete control over all parameters, the Bright Search Interface, which leaves to the user the possibility to tune parameters for alignment of spectra, and the Quick Search Interface, which limits the number of parameters to a minimum by using default values for the majority of parameters. Geena 2 has been utilized, in conjunction with a statistical analysis tool, in three published experimental works: a proteomic study on the effects of long-term cryopreservation on the low molecular weight fraction of serum proteome, and two retrospective serum proteomic studies, one on the risk of developing breat cancer in patients affected by gross cystic disease of the breast (GCDB) and the other for the identification of a predictor of breast cancer mortality following breast cancer surgery, whose results were validated by ELISA, a completely alternative method. Conclusions Geena 2 is a public tool for the automated pre-processing of MS data originated by MALDI/TOF instruments, with a simple and intuitive web interface. It is now under active development for the inclusion of further filtering options and for the adoption of standard formats for MS spectra.

Purpose The aim of the study was to correlate nuclear matrix (NM) protein expression profiles with the risk of PSA progression or death in early prostate cancer (PCa). Methods High-resolution two-dimensional gel electrophoresis (2D-PAGE) was used to identify tumor-associated NM proteins in the PCa specimens obtained from 94 patients. The association between the expression of each protein and the probability of PSA progression or death was studied through univariate analysis. Unsupervised hierarchical clustering analysis was then used to generate patient clusters showing comparable outcomes by including the proteins that were predictive at univariate analysis. PSA-free and overall survival curves relative to each cluster were constructed by means of the Kaplan–Meier method and curves compared by the log-rank test. Multi-parametric models were constructed according to Cox proportional hazard technique. Results After a median follow-up of 11.7 years (range, 6.5–16.2), 50 patients progressed and 22 died. Of the eight NM proteins identified through 2D-PAGE, proteins NM-6, NM-7 and NM-8 were confirmed to be individually associated with a higher risk of PSA progression at univariate analysis. Proteins NM-6 and NM-8 were also predictive of survival probability. Hierarchical clustering analysis of these proteins allowed to identify one cluster of tumors co-expressing the three proteins or proteins NM-6 and NM-8, characterized by a very poor outcome, suggesting a specific role for these proteins in PCa progression. The predictive value of this mini-signature in respect to PSA-free survival was confirmed by multivariate analysis. Conclusions Changes in NM scaffolding are strongly associated with the clinical outcome of patients following radical prostatectomy.